Breast cancer is the most frequent cancer in women and is the second leading cause of cancer-related death and the present breast cancer therapies achieve meaningful clinical results in only 30-40% of patients. (F. Labrie et al., J. Steroid Biochem. Mol. Biology, 69 51-84 (1999)). Estrogens are well recognized to play the predominant role in breast cancer development and growth and much effort has been devoted to the blockade of estrogen formation and action (V. C. Jordan and W. J. Gradishar, Molec. Aspects Med., 18, 187-247 (1997)). However, expression of the HER-2 receptor is also a significant factor associated with breast cancer morbidity. (D. J. Slamon, et al, Science, 244, 707-712, (1989)). It is also becoming clearer that crosstalk between estrogen and growth factor receptor pathways occurs and likely is a factor in the pathology and treatment of breast cancer. (Y. Kinoshita and S. Chen, Cancer Res., 63, 3546-3555, (2003))
The most widely used therapy for breast cancer, which has shown benefits at all stages of the disease, is the use of an antiestrogen such as tamoxifen. Over thirty years of clinical trials with tamoxifen have not only proven its clinical merits but also highlighted the need for a next generation of drugs that are potentially more efficacious and have fewer side-effects, especially the serious side-effects related to estrogen agonist properties (K. Dhingra, Investigational New Drugs 17, 285-311 (1999))
“Tanshen”, the rhizome of Salvia miltiorrhiza Bunge, has been used in traditional Chinese medicine (TCM) for the treatment of coronary heart diseases, particularly angina pectoris and myocardial infarction. It has also been applied for hemorrhage, dismenorrhea, miscarriage, swelling, and insomnia (S. Y. Ryu et al., Planta Medica, 63, 339-342 (1997)). Neo-tanshinlactone (1) was originally isolated from this TCM. Its structure is unique compared to those of other constituents isolated from S. miltiorrhiza. 